High-frequency oscillatory ventilation on shaky ground.

We thought it was impossible. Physiological principles maintained that ventilation at tidal volumes less than the anatomical deadspace should be ineffective (i.e., inspired air not reaching the alveolae). Data from a 1980 study dispelled that myth, showing unequivocally that ventilation with tidal volumes as small as 20 to 30 ml in dogs, a mere fraction of the anatomical deadspace, could maintain adequate ventilation.1 These unexplained observations sparked transport and mixing theories predicting that CO2 removal should vary in direct proportion to breathing frequency (although the relationship with tidal volume is more complex2,3), and these predictions were later confirmed experimentally.4 Subsequent studies showed that CO2 removal eventually reaches a plateau when the airways narrow during expiration, indicating the onset of expiratory-flow limitation. This concept is important, since portions of the lung can become hyperinflated dynamically (i.e., regional air trapping) beyond levels predicted from the applied mean airway pressure.5-7 High-frequency oscillatory ventilation (HFOV), in which small tidal volumes are applied at a high respiratory rate, became a focus of research and clinical practice, but widespread use was limited by the unavailability of commercial equipment. As the technology gradually evolved, the field suffered setbacks when trials showed that HFOV did not provide a benefit and could have induced harm in neonates with the respiratory distress syndrome.8,9 Although there have been some small clinical trials,10 the use of HFOV in adult patients never really caught on. More and better data were needed, and the field evolved as our understanding of the physiology of the acute respiratory distress syndrome (ARDS) improved. Although mechanical ventilation can clearly be life-sustaining for those who are critically ill, there are now compelling data showing that mechanical ventilation can be damaging to the lung if the ventilator is set inappropriately. Excessive tidal volumes can stretch the lung, leading to overdistention and further lung injury.11 Inadequate positive end-expiratory pressure (PEEP) can promote repetitive alveolar collapse followed by reopening, which may be injurious to the lung (an injury known as atelectrauma). Lung homogeneity is also thought to be important, since injurious forces can develop at junctions of normal and abnormal lung even when the applied pressures are modest.12 Thus, in theory, HFOV in a well-recruited, homogeneous lung could avoid these problems if the problems with local airflow velocity could be overcome. If so, HFOV could combine small pressure oscillations to minimize overdistention with high mean airway pressures to prevent atelectrauma (Fig. 1). Two major, multicenter, randomized trials now reported in the Journal show that it is hard to put theory into practice. In the Oscillation for Acute Respiratory Distress Syndrome Treated Early (OSCILLATE) trial,14 the authors found that an HFOV strategy with high mean airway pressures led to more deaths than did a conventional mechanical-ventilation strategy that used relatively high PEEP levels. Patients in both groups underwent a baseline recruitment maneuver (sustained high-pressure inflation) to promote lung homogeneity. In-hospital mortality was 47% in the HFOV group as compared with 35% in the control group (relative risk of death with HFOV, 1.33; 95% confidence interval, 1.09 to 1.64; P = 0.005), a finding that led to premature termination of the trial. The mechanism underlying the poor HFOV outcomes appears to